Thrombin Activity by Intrinsic Activation of Plasma In-Vitro Accelerates with Increasing Age of the Donor

Ibbotson, S H; Tate, G. M.; Davies, J. A.

doi:10.1055/s-0038-1648450

Cited by 24 publications

(16 citation statements)

References 14 publications

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“…It is known that the increase in age is one of risk factors for thrombus formation [46]. It is reported that the levels of fibrinogen, F-VII, F-VIIII, and F-IX increase with age [47,48]. In our experiments [14], it was shown that coagulation of blood was enhanced with age ( Fig.…”

Section: Evaluation Of Enzymatic Activity Of Rbcs By Fluorescence Measupporting

confidence: 59%

Rheological study on coagulation of blood with special reference to the triggering mechanism of venous thrombus formation

Kaibara

2009

J Biorheol

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A markedly reduced blood flow, an elevation of hematocrit and an increased aggregability of erythrocytes [red blood cells (RBCs)] are risk factors for venous thrombus formation (intravascular blood coagulation). However, these risk factors alone seem to be insufficient to stimulate the coagulation cascade in the absence of a primary triggering mechanism. In this paper, our rheological and biochemical studies on blood coagulation, especially focusing on procoagulant activity of RBCs, are summarized. It is shown that the intrinsic coagulation pathway is triggered by the activation of factor IX (F-IX) by RBCs. The F-IX-activating enzyme in normal human erythrocyte (RBC) membranes was purified, identified and characterized. The activation of F-IX by RBCs was enhanced by a decrease in flow shear rate and an elevation in hematocrit. The procoagulant ability of RBCs and coagulation of blood obtained from individuals with a relatively high level of hypercoagulability were enhanced compared with those for normals. The studies demonstrated a new triggering mechanism for coagulation or thrombus formation that may occur under stagnant flow conditions.

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Section: Evaluation Of Enzymatic Activity Of Rbcs By Fluorescence Measupporting

confidence: 59%

Rheological study on coagulation of blood with special reference to the triggering mechanism of venous thrombus formation

Kaibara

2009

J Biorheol

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“…It is reported that the levels of fibrinogen, factor VII, factor VIII, FIX, high molecular weight-kininogen and prekallikrein increase with age [34][35][36][37]. The fluorescence intensity of a mixture of RBCs and the fluorogenic substrate, which may be related to the enzymatic activity, was higher at older age.…”

Section: Discussionmentioning

confidence: 99%

Rheological analyses of coagulation of blood from different individuals with special reference to procoagulant activity of erythrocytes

Kaibara

Iwata

Ujiié

et al. 2005

Blood Coagulation &Amp; Fibrinolysis

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In our previous papers, we reported that factor IX (FIX), when activated by erythrocyte membranes, causes coagulation. We have identified and characterized the FIX-activating enzyme located in normal human erythrocyte membranes. In this paper, to examine physiological and pathological significances of procoagulant activity of erythrocytes, coagulation of blood obtained from different individuals was analyzed by means of a rheological technique. In more than 65% of subjects including normals and patients, the initiation of coagulation seemed to be governed by erythrocytes. Coagulation of whole blood and platelet-free plasma supplemented with erythrocytes had a tendency to occur rapidly in the elderly. It was suggested that the concentration of FIX-activating enzyme on erythrocyte membranes for aged donors was somewhat higher than that for young ages. Propagation reactions on erythrocyte membranes (i.e. factor X activation leading to thrombin generation after FIX activation) was slower than that on platelet membranes. Moreover, the propagation reaction on erythrocyte membranes was greatly dependent on individuals, whereas that on platelet membranes was not so much. Our study demonstrates that the activation of FIX by erythrocytes and subsequent propagation reaction on platelet membranes may be important for initiating and controlling blood coagulation reactions.

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“…11,15 Evidence indicates that coagulation rates in plasma are accelerated with age, 16 which suggests the hematoma can produce much more thrombin in aging rats. It is important to know whether the effect of thrombin inhibition would also be age dependent.…”

Section: Physiological Parameters*mentioning

confidence: 99%

Intracerebral Hemorrhage

Gong

Hua

Keep

et al. 2004

Stroke

128

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Background and Purpose-Intracerebral hemorrhage (ICH) is mostly a disease of the elderly, but most current experimental ICH models have used young animals. Age is an important factor in other forms of brain injury, affecting microglia and astrocyte reactions and plasticity. Therefore, the present study investigated the effects of aging on brain injury after ICH. Methods-Young and aged (3 and 18 months old, respectively) male Sprague-Dawley rats received an intracerebral infusion of 100 L autologous blood. Age-related changes in brain swelling, glial reaction, stress protein (heat shock proteins [HSPs] 27 and 32), and neurological deficits were examined. Results-Brain swelling was more severe in old rats compared with young rats at 3 days after ICH (PϽ0.05). There were also more severe neurological deficits in the older rats at 1 day after ICH, which persisted for the 4 weeks of monitoring (PϽ0.05). The older rats also had stronger microglial activation and a greater perihematomal induction of HSP-27 and HSP-32 (PϽ0.05). In contrast, there was a weaker astrocytic reaction to the hematoma. Conclusions-ICH causes more severe brain swelling and neurological deficits in old rats. Clarification of the mechanisms of brain injury after ICH in the aging brain should help develop new therapeutic strategies for hemorrhagic brain injury.

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Thrombin Activity by Intrinsic Activation of Plasma In-Vitro Accelerates with Increasing Age of the Donor

Cited by 24 publications

References 14 publications

Rheological study on coagulation of blood with special reference to the triggering mechanism of venous thrombus formation

Rheological study on coagulation of blood with special reference to the triggering mechanism of venous thrombus formation

Rheological analyses of coagulation of blood from different individuals with special reference to procoagulant activity of erythrocytes

Intracerebral Hemorrhage

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